Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Cough sound-based estimation of vital capacity via cough peak flow using artificial neural network analysis

Abstract This study presents a novel approach for estimating vital capacity using cough sounds and proposes a neural network-based model that utilizes the reference vital capacity computed using the lambda-mu-sigma method, a conventional approach, and the cough peak flow computed based on the cough sound pressure level as inputs. Additionally, a simplified cough sound input model is developed, with the cough sound pressure level used directly as the input instead of the computed cough peak flow. A total of 56 samples of cough sounds and vital capacities were collected from 31 young and 25 elderly participants. Model performance was evaluated using squared errors, and statistical tests including the Friedman and Holm tests were conducted to compare the squared errors of the different models. The proposed model achieved a significantly smaller squared error (0.052 L2, p < 0.001) than the other models. Subsequently, the proposed model and the cough sound-based estimation model were used to detect whether a participant’s vital capacity was lower than the typical lower limit. The proposed model demonstrated a significantly higher area under the receiver operating characteristic curve (0.831, p < 0.001) than the other models. These results highlight the effectiveness of the proposed model for screening decreased vital capacity

A Mobile Cough Strength Evaluation Device Using Cough Sounds

Although cough peak flow (CPF) is an important measurement for evaluating the risk of cough dysfunction, some patients cannot use conventional measurement instruments, such as spirometers, because of the configurational burden of the instruments. Therefore, we previously developed a cough strength estimation method using cough sounds based on a simple acoustic and aerodynamic model. However, the previous model did not consider age or have a user interface for practical application. This study clarifies the cough strength prediction accuracy using an improved model in young and elderly participants. Additionally, a user interface for mobile devices was developed to record cough sounds and estimate cough strength using the proposed method. We then performed experiments on 33 young participants (21.3 &#177; 0.4 years) and 25 elderly participants (80.4 &#177; 6.1 years) to test the effect of age on the CPF estimation accuracy. The percentage error between the measured and estimated CPFs was approximately 6.19%. In addition, among the elderly participants, the current model improved the estimation accuracy of the previous model by a percentage error of approximately 6.5% (p &lt; 0.001). Furthermore, Bland-Altman analysis demonstrated no systematic error between the measured and estimated CPFs. These results suggest that the developed device can be applied for daily CPF measurements in clinical practice

Estimation of Cough Peak Flow Using Cough Sounds

Cough peak flow (CPF) is a measurement for evaluating the risk of cough dysfunction and can be measured using various devices, such as spirometers. However, complex device setup and the face mask required to be firmly attached to the mouth impose burdens on both patients and their caregivers. Therefore, this study develops a novel cough strength evaluation method using cough sounds. This paper presents an exponential model to estimate CPF from the cough peak sound pressure level (CPSL). We investigated the relationship between cough sounds and cough flows and the effects of a measurement condition of cough sound, microphone type and participant&rsquo;s height and gender on CPF estimation accuracy. The results confirmed that the proposed model estimated CPF with a high accuracy. The absolute error between CPFs and estimated CPFs were significantly lower when the microphone distance from the participant&rsquo;s mouth was within 30 cm than when the distance exceeded 30 cm. Analysis of the model parameters showed that the estimation accuracy was not affected by participant&rsquo;s height or gender. These results indicate that the proposed model has the potential to improve the feasibility of measuring and assessing CPF